We propose to develop a manufacturing process in compliance with current Good Manufacturing Practices (cGMP) for the production of tumor antigen-loaded, autologous dendritic cell (DC) derived dexosomes, a candidate immunotherapeutic vaccine, that will permit its clinical evaluation for the treatment of colon cancer. In preliminary studies, tumor antigen-pulsed DC have been shown to secrete antigen-loaded lipid vesicles, referred to as dexosomes. When such dexosomes were purified and administered systemically to animals harboring pre-established tumors, a dramatic cellular immune response was evoked which suppressed tumor growth and eliminated tumor completely in a significant fraction of the animals treated This response to dexosomes was superior to that of antigen-pulsed DC themselves thus dexosomes may represent a more efficacious immunotherapeutic tumor vaccine than live DC in addition to representing a potentially simpler target for commercial development. The goal of this development project is to transform the current laboratory process into a clinical grade manufacturing process such that clinical grade raw materials, roper documentation, a reproducible and qualified process and quality control testing are all incorporated The successful completion of this Phase I proposal will permit clinical evaluation of this candidate immunotherapeutic and potential support by an SBIR Phase II award. PROPOSED COMMERCIAL APPLICATION: The need is immense for the development of new treatments for metastatic cancer. For instance in the US alone, 155,000 new cases of colorectal cancer are diagnosed and approximately 50% of these patients will die from metastatic disease. The cost of treatment of these patients exceeds $10 billion each year and thus new therapies must be developed to treat these patients more effectively and at lower total cost to society. The development program proposed herein will directly address this need by advancing to a clinically evaluable stage the novel technology of dexosome based immunotherapeutic vaccines for cancer. It should he noted that development efforts described here for dexosome based tumor immunotherapy using CEA as a target antigen for colorectal cancer will also be applicable to other cancers by substituting a tumor antigen relevant for that disease.